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At least 379 records · Page 21Linked to original sources
PubMed2003

Experimental autoimmune encephalomyelitis: cytokines, effector T cells, and antigen-presenting cells in a prototypical Th1-mediated autoimmune disease.

Experimental autoimmune encephalomyelitis (EAE) is widely depicted as the prototypical CD4+ Th1-mediated autoimmune disease. Microglia and perivascular macrophages are believed to act as antigen-presenting cells during the effector phase of EAE. In this article, recent data that challenge these conceptions are reviewed. Several recent studies have shown that myelin-reactive CD8+ T cells can mediate inflammatory demyelination. Furthermore, dendritic-like cells have been detected in EAE lesions and implicated in encephalitogenic T-cell activation. Although Th1 polarizing monokines, such as interleukin-12 (IL-12) and possibly IL-23, are critical for the manifestation of EAE, individual Th1 effector cytokines were found to be dispensible.

Animals↗
PubMed1980

Evaluation of ischemic heart disease with a prototype volume imaging computed tomographic (CT) scanner: preliminary experiments.

A prototype synchronous volumetric computed tomographic X-ray scanner was used to demonstrate, in individual experiments, the possibility of estimating percent coronary arterial stenosis, regional myocardial blood supply and regional myocardial wall dynamics. Scans were obtained during angiography in intact anesthetized dogs or in an isolated metabolically supported working left ventricular preparation. Percent arterial stenosis was quantitated using the percent change in brightness area product of successive cross-sectional images of contrast agent-filled Tygon tubing sutured to the epicardium. Myocardial blood supply was evaluated by the transmural and circumferential extent and th time rate of change of myocardial opacification during coronary angiography. The regional time rate of change of left ventricular wall thickening during the systolic phase of the cardiac cycle was demonstrated in the isolated ventricle preparation. The recently installed Dynamic Spatial Reconstructor high speed volumetric scanning system will be used to make these measurements from scan data obtained during a single angiogram in man.

Animals↗
PubMed1984

Polymyositis and interstitial lung disease in a patient with anti-Jo1 prototype.

The most common marker autoantibody among patients with polymyositis is anti-Jo1. The patient (John P.) providing the prototype serum for this specificity had both interstitial lung disease and polymyositis. A preliminary survey by Ouchterlony analysis and counter immunoelectrophoresis of serum from 15 patients with idiopathic interstitial lung disease revealed no anti-Jo1 or other precipitating autoantibodies. This provides no evidence to suggest that anti-Jo1 has specificity for interstitial lung disease per se. However, this autoantibody may serve as a possible marker for some patients with overlap of polymyositis and interstitial lung disease. The several interesting features about this patient's diseases and course are discussed.

Antibody Specificity↗
PubMed1989

Stopped-flow front-face fluorometer: a prototype design to measure hemoglobin R----T transition kinetics.

Stopped-flow techniques are successfully used to study the kinetics of the R----T transition of hemoglobin (Hb). We have previously used front-face fluorometry to demonstrate that (i) the intrinsic fluorescence of Hb primarily originates from beta 37 Trp; (ii) the intrinsic fluorescence is sensitive to the R----T transition; and (iii) the emission of the fluorescent probes bound to specific sites on the Hb molecule (beta 93 Cys) is sensitive to the R----T transition. These findings suggested that a stopped-flow front-face fluorometer could probe R----T transitions at specific sites, such as the aromatic amino acids and sites selectively binding extrinsic fluorophores. We have developed a prototype instrument using as the core a Gibson-Durrum stopped-flow apparatus on line with a digital data analysis system using a modified Marquardt algorithm. Excitation (470 nm) and emission light (520 nm) were selected by narrow band pass filters. To study the R----T transition, a solution of purified oxy Hb A covalently bound to the fluorescent probe 5-iodoacetamidofluorescein (Hb A-AF) (1.0 g%) was mixed rapidly with deoxygenated buffer (pH 7.35, 0.05 M potassium phosphate) containing 2 mg/ml of sodium dithionite. The hemoglobin, at a final concentration of 0.5 g% after mixing, is essentially completely tetrameric. A first-order reaction was observed with a rate constant near 8 s-1, similar to the oxygen dissociation rate reported for oxy Hb A.(ABSTRACT TRUNCATED AT 250 WORDS)

Algorithms↗
PubMedDate not supplied

Comparative chemical and biological studies of four prototype phosphoraziridine antineoplastic agents.

The chemical alkylating activities of four prototype phosphoraziridine antineoplastic agents were compared with their biological effects on V-79 Chinese hamster lung fibroblasts. It was found that the chemical reactivity patterns correlate well with all of the biological parameters examined in this study, i.e. cytotoxicity, DNA synthesis, and production of alkali labile strand breaks. Specifically, the 2,2-dimethylaziridine derivatives (AB-132 and AB-163) showed higher initial activities reaching a plateau after a short reaction time in all of the systems used in this study while the unsubstituted aziridine derivatives (AB-100 and D-63) reacted more slowly but continued to exert their action in a linear fashion to produce greater overall effects. These findings are consistent with the conclusion that the difference between the time-dependent biological activities of these drugs closely follows the different chemical mechanisms of their alkylating reactions (SN1 vs SN2). The more rapid action and subsequent hydrolytic inactivation of the 2,2-dimethylphosphoraziridines as effective alkylators could be the basis of their lower hemopoietic toxicity compared to conventional alkylating agents including their own C-unsubstituted aziridine analogs. The much more rapid action of the 2,2-dimethylphosphoraziridines on DNA inside the cell may have some bearing on their radiation potentiating activity, but this aspect and the cholinesterase inhibitory activity of these agents (which may depend on phosphorylation) were not investigated in the present study.

Alkylating Agents↗
PubMed1975

A prototype segmental model for blood flow and heat transfer in the limb.

A general modeling technique for characterizing the blood flow and heat tranfer properties in the human limb is reported in this paper. The basic idea is to take the segmental approach so that a lumped model for each segment can be constructed. Consequently, a prototype segmental computer model is proposed which describes, in general terms, the interrelationships between the circulatory system and the thermal system of the limb. Simulation study of digital response to hand cooling is made and the results agree very well with the experimental data.

Body Temperature Regulation↗
PubMed1987

Psyxpert: an expert system prototype for aiding psychiatrists in the diagnosis of psychotic disorders.

Psyxpert is an expert computer system prototype designed to aid psychiatrists in the diagnosis of mental disorders, in cases where psychotic features are the prominent part of the presenting clinical picture. The knowledge base contains psychiatric knowledge in the form of production rules. The system uses a backward-chaining control strategy to guide the consultation. Psyxpert provides a menu-driven user interface and an explanation subsystem. The system uses certainty and importance measures to produce a diagnosis with an attached certainty factor and recommendations for further evaluation or therapy. Psyxpert is written in Virginia Tech HC Prolog and runs on Digital Equipment Corporation's VAX 11/780 under the VMS operating system.

Computer Systems↗
PubMed1993

Pilot trial of a gonadotropin hormone agonist with replacement hormones as a prototype contraceptive to prevent breast cancer.

Combination oral contraceptive (COC) users have reduced risks of ovarian and endometrial cancer, but COCs have not reduced breast cancer risk. We have previously argued that a hormonal contraceptive with substantially lower doses of sex-steroids should reduce breast cancer risk by decreasing the breast epithelial cell proliferation below usual premenopausal levels. We report here the preliminary results of a pilot trial with such a prototype contraceptive consisting of an agonist of gonadotropin releasing hormone (GnRHA) administered with low doses of an oral estrogen (0.625 mg of conjugated estrogen, CE, for 6 days every week) and intermittent oral progestogen (10 mg of medroxyprogesterone acetate, MPA, for 13 days every 4 months). Eighteen subjects at five-fold or greater increased breast cancer risk were entered and randomized -12 to the contraceptive arm and 6 to a control arm. The principal endpoints included tolerance of the regimen, vaginal bleeding patterns, and the regimen's effect on the endometrium, bone metabolism, and lipids. A symptom questionnaire was used to assess tolerance; the contraceptive subjects had fewer symptoms following initiation of the regimen. This results from the elimination of symptoms associated with the luteal phase of the menstrual cycle, commonly referred to collectively as premenstrual syndrome, PMS. The few occurrences of hot flushes or vaginal dryness that did occur were eliminated by small increases in estrogen dose (0.9 mg CE). Scheduled vaginal bleeding occurred associated with most periods of progestogen administration. Unscheduled bleeding or spotting was infrequent and decreased with time on the regimen. A beneficial rise in high-density lipoprotein cholesterol was evident in the contraceptive subjects. Despite the use of an estrogen dose which is known to prevent loss of bone mineral density in normal postmenopausal women, an annualized loss of 1.9% was seen in contraceptive subjects. It is hypothesized that this is secondary to inhibition of ovarian androgen production by the GnRHA, which may additionally account for changes in libido occasionally reported with GnRHA. The study continues with the addition of a small dose of androgen to replace that lost by the action of the GnRHA.

Adult↗
PubMed1984

Is methylnalorphinium the prototype of an ideal peripheral analgesic?

Oral methylnalorphine ( methylnalorphinium ) caused a dose-dependent selective inhibition of inflammatory hyperalgesia (measured in the rat by a modified version of the Randall- Selitto test) without affecting the oedema. When subcutaneously injected, repeated doses of morphine for 5 days caused progressive analgesic tolerance. Tolerance was not observed after similar treatment with methylnalorphinium or methylmorphinium . Animals displaying analgesic tolerance to systemic morphine did not exhibit tolerance to the local ( intraplantar ) injection of morphine, methylnalorphinium or methylmorphinium . In contrast with nalorphine and other opiates, methylnalorphinium did not reduce intestinal transit in mice. Methylnalorphinium , a mixed opiate agonist-antagonist devoid of central effects, might be considered the prototype of an ideal peripheral analgesic since it was orally active, did not affect intestinal transit and did not cause analgesic tolerance.

Analgesics↗
PubMed1978

Clinical evaluation of a prototype intraoral source x-ray system.

A prototype dental roentgenographic system which incorporates a tightly collimated intraoral x-ray source and an extraoral Polaroid film screen cassette was evaluated both in vitro and in vivo. Findings indicate that the detectability of artificially induced incipient enamel lesions was significantly less than that demonstrable for conventional roentgenograms produced with an extraoral source, long-cone geometry, and Kodak Ultra Speed D film. Larger lesions were found to be reliably detected by either technique. The new intraoral approach reduces the dose to the patient by possibly as much as 98 per cent and yields positive dry prints in 15 seconds. This system was clinically tested and found to be useful in endodontics and presurgical evaluation. Modifications are discussed which could reduce some of the technical problems and many of the shortcomings encountered.

Acid Etching, Dental↗
PubMed1987

The genetic animal model of reflex epilepsy in the Mongolian gerbil: differential efficacy of new anticonvulsive drugs and prototype antiepileptics.

Four new anticonvulsive drugs were compared to four prototype antiepileptics regarding their differential efficacy, i.e. against tonic-clonic, myoclonic, and minor seizures, in reflex epilepsy in genetically epileptic gerbils. We distinguished at least three types of drugs: Phenytoin and ralitoline selectively prevented tonic-clonic seizures; the other drugs tested were active against all seizure types. However, carbamazepine and AHR-11748 were predominantly active against tonic-clonic seizures, whereas phenobarbital, valproate, gabapentin, and zonisamide equipotently suppressed both tonic-clonic and myoclonic seizures.

Animals↗
PubMed1993

Alteration in proliferative and endocrine responsiveness of human mammary carcinoma cells by prototypic tumor-suppressing agents.

The experiments performed in this study were designed to establish that (1) acquisition of anchorage-independent growth, a biological characteristic of tumorigenically transformed phenotype, can be modulated by prototypic tumor-suppressing agents, and (2) modulation of growth is influenced by the metabolic competence of the cells to biotransform estradiol, MCF-7 human breast carcinoma cells exhibited linear cell proliferative kinetics with a 41-hour population doubling time, and a 15% colony-forming efficiency in 0.33% agar. Indole-3-carbinol (13C), a naturally occurring tumor-suppressive agent; tamoxifen (TAM), an antiestrogenic agent; and 4-hydroxytamoxifen (4-OHTAM), a metabolite of TAM, demonstrated 73.7%, 72.5%, and 89.9% suppression in anchorage-independent growth of MCF-7 cells, respectively. At the metabolic level, 13C and 4-OHTAM induced 2.3-fold (P < 0.0001) and 1.3-fold increase (P = 0.001) relative to their own controls in the extent of 2-hydroxylation of estradiol. The results indicate that growth inhibition by 13C, TAM, and 4-OHTAM may in part be due to altered estradiol metabolism in MCF-7 cells. Thus, anchorage-independent growth and altered biotransformation of estradiol may constitute useful cellular and endocrine markers to evaluate the biological response of chemosuppressive agents.

Antineoplastic Agents↗
PubMed1985

A putative transforming gene of Jijoye virus differs from that of Epstein-Barr virus prototypes.

The P3HR-1 strain of Epstein-Barr virus (EBV), a nontransforming clonal derivative of Jijoye (EBV), is characterized by a deletion of 6.6 kb involving part of the BamHI-W repeats and the adjacent region including the NotI repeats. In the transforming parental Jijoye virus this region differs from the corresponding regions in B95-8 or M-ABA virus. The HindIII-B fragments which carry this region from both Jijoye and prototype M-ABA (EBV) viruses have been cloned and subclones have been constructed which contain the left-hand part of HindIII-B from the HindIII to the BglII site (BglII-delta C fragment). By restriction enzyme analysis the inserts were found to be of equal size (6.3 kb) but to differ in their restriction enzyme pattern. Heteroduplexes formed under stringent conditions in the presence of T4 gene 32 protein revealed a substitution loop of 1750 +/- 200 nucleotides. Heteroduplex formation under nonstringent conditions showed that the substituted sequences are partially homologous to each other, with the regions of nonhomology confined to three distinct areas of 100 to 200 nucleotides. The partial homology observed between both regions indicates that they have evolved from a common ancestor. By hybridization of a Jijoye virus subclone containing only sequences of the substituted region to Northern blots a 2.8-kb polyadenylated transcript was detected indicating that the substituted region is expressed in Jijoye cells.

Cell Line↗
PubMed1987

The genetic relatedness of United States prototype bluetongue viruses by RNA/RNA hybridization.

The genetic relatedness of the prototype bluetongue viruses isolated in the United States was examined by RNA/RNA hybridization. Genomic dsRNAs of bluetongue viruses were separated by either SDS-PAGE or NuSieve agarose gel electrophoresis and were blotted by both standard Northern technique and the recently developed rapid alkali-blotting method of Li, Kowalik, and Parker (submitted for publication) to positively charged nylon membranes. The blotted RNA was then probed with 3'-end-labeled dsRNA of each serotype. Initially, single segments were individually hybridized to identify cognate genes. Total genomic dsRNAs were then probed to determine genetic relatedness. The genes coding for the nonstructural proteins NS1 and NS2 were the most conserved. Most of the RNA segments coding for the core proteins were also well conserved, with segment S1 showing some diversity among the five serotypes. The outer capsid protein-coding segments demonstrated a wide degree of sequence divergence with segment L2 having little or no cross-hybridization among the five serotypes.

Bluetongue virus↗
PubMedDate not supplied

Amyloid typing using antisera to prototype fibril proteins. A brief note.

Amyloid fibril proteins from three patients with generalized amyloidosis were isolated and chemically characterized by N-terminal amino-acid sequence studies in two of them. As they belonged to three different amyloid classes they served as prototypes for the preparation of antisera specific for each class. Using these antisera in immunodiffusion, amyloid fibril proteins of 15 additional cases with generalized amyloidosis have been investigated. These could be grouped into four categories: seven belonging to the amyloid A type, three to the amyloid L, lambda type, and three to the amyloid L, kappa type; the amyloid fibril proteins of two patients could not be classified by these agents and may represent still unidentified amyloid types.

Amyloid↗
PubMed1996

Comparison of the effects of prototypical behavioral stimulants on locomotor activity and rotational behavior in rats.

The present study was performed to characterize on rotational behavior the dose- and time-effect relationship of four prototypical behavioral stimulants that interact with dopamine systems via different mechanisms of action. Drug effects on rotational behavior was compared with effects on locomotor activity. The drugs examined were apomorphine (0.03-1.0 mg/kg), d-amphetamine (0.1-3.0 mg/kg), cocaine (3.0-56 mg/kg), and caffeine (10-100 mg/kg). SKF-38393 (0.3-10 mg/kg), a dopamine receptor agonist that has only modest effects on locomotor activity, was tested as a comparison. In rats with unilateral 6-hydroxydopamine (6-OHDA)-induced lesions of the nigrostriatal tract, d-amphetamine and cocaine dose dependently increased both the duration and the maximum number of turns/10 min, whereas apomorphine and caffeine increased only the duration of turning. There was a significant correlation of the effects of the four drugs on rotational behavior with effects on locomotor activity, but effects across drugs were not identical. Dose-response curves revealed potency differences among drugs in their effects on the two behaviors (e.g., apomorphine stimulated rotational behavior at a lower dose than it stimulated locomotor activity, whereas the converse was true with caffeine). Different mechanisms of action of these drugs might account for the differences in their effects on these behaviors.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1980

DNA of Epstein-Barr virus VIII: B95-8, the previous prototype, is an unusual deletion derivative.

B95-8, an infectious mononucleosis-derived isolate of Epstein-Barr virus (EBV), is biologically and antigenically indistinguishable from other isolates of EBV and has been the prototype for previous studies of EBV DNA. The long unique region UL of the DNA of a Burkitt tumor isolate, W91, is 9 X 10(6) daltons longer than the UL of B95-8. The "additional DNA and the regions around it have been cloned from W91 and another Burkitt tumor isolate, AG876. The additional DNA is viral and not cellular, since W91 and AG876 have almost identical additional DNA, and there is no detectable homology to human lymphocyte DNA. The insertion site of the additional DNA is within the 0.96 X 10(6) dalton Hinf 1 fragment of B95-8 Bam Hl l. After infection and transformation of five cell lines B95-8 did not pick up additional DNA in this region. Hybridization of labeled DNAs from three EBV-infected cell lines derived from patients with infectious mononucleosis to blots of fragments of the additional DNA indicates that these sequences are present in American as well as in African virus. B95-8 is therefore an unusual deletion derivative. A newly discovered feature of EBV DNAs is that sequences which map near the left end of UL have homology to part of the additional DNA.

Animals↗
PubMed1987

Space motion sickness preflight adaptation training: preliminary studies with prototype trainers.

Preflight training frequently has been proposed as a potential solution to the problem of space motion sickness. The paper considers successively the otolith reinterpretation, the concept for a preflight adaptation trainer and the research with the Miami University Seesaw, the Wright Patterson Air-Force Base Dynamic Environment Simulator and the Visually Coupled Airborne Systems Simulator prototype adaptation trainers.

Adaptation, Physiological↗